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Neuropsychiatric symptoms (NPS) are non-cognitive manifestations common to dementia and other medical conditions, with important consequences for the patient, caregivers, and society. Studies investigating NPS in individuals with Down syndrome (DS) and dementia are scarce. Characterize NPS and caregiver distress among adults with DS using the Neuropsychiatric Inventory (NPI). We evaluated 92 individuals with DS (≥30 years of age), divided by clinical diagnosis stable cognition, prodromal dementia, and AD. Diagnosis was determ